Hormone Therapy Doesn’t Increase Mortality in Postmenopausal Women

​​By staff

Boston—Whatever the other controversies surrounding use of hormone therapy in postmenopausal women, an estrogen-progestin combination or estrogen alone do not appear to affect total mortality or deaths from cardiovascular disease, cancer, or other major illnesses.

That’s according to a study in JAMA based on the Women’s Health Initiative (WHI) hormone therapy trials. Brigham and Women’s Hospital researchers note that earlier reports did not focus specifically on all-cause mortality and cause-specific mortality.

Their new study, however, is the first to examine the long-term rates of death from all causes and the rates of death from specific causes, including cardiovascular disease, cancer, and other major illnesses over an 18-year follow-up of 27,347 women from the two WHI hormone-therapy trials.

The results? In women ages 50 to 79 years, researchers found no increase or decrease in total mortality.

“All-cause mortality provides a critically important summary measure for an intervention such as hormone therapy that has a complex matrix of benefits and risks,” explained lead author JoAnn Manson, MD, DrPH, chief of the Division of Preventive Medicine at BWH.

“Mortality rates are the ultimate ‘bottom line’ when assessing the net effect of a medication on serious and life-threatening health outcomes.”

Past studies have found both benefits to hormone therapy—such as reducing hot flashes and menopausal symptoms, and decreasing the incidence of hip and other fractures—and risks, including venous blood clots, stroke, and certain cancers.

“In this new analysis, we found that there was no association between hormone therapy and all-cause mortality during either the treatment period or the long-term follow-up of these trials,” Manson said.

To come to that conclusion, the study team analyzed data from the two trials, which included postmenopausal women with an average age of 63 at enrollment. During follow-up, 7,489 deaths occurred, more than twice as many deaths as were included in earlier reports with shorter follow-up periods.

When examined by 10-year age groups, mortality outcomes were found to be more favorable among younger women who received hormone therapy versus older women also receiving the therapy.

During the 5 to 7 years of treatment, the death rates in the women aged 50 to 59 years generally were about 30% lower among women who received hormone therapy compared with women of the same age who received placebo, but, among women who initiated hormone therapy in their 60s and 70s, no effect on death rate was observed.

After 18 years, which included 10 to 12 years of follow-up after discontinuing hormone therapy, the differences by age group diminished and were no longer statistically significant, researchers point out.

While overall mortality rates and deaths from cardiovascular disease and cancer were neither increased nor decreased among the intervention group, researchers also determined that deaths from Alzheimer’s disease and other forms of dementia were significantly lower with estrogen-alone group than in the placebo group during 18 years of follow-up, although use of estrogen plus progestin was not associated with dementia mortality.